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Objective : The objectives of the study were to estimate the perfusion of tumors by drugs used in intra-arterial chemotherapy of head and neck cancer with magnetic resonance imaging (MRI) and to establish the factors involved in determining the optimal dose. Study Design : Contrast agent was administered intra-arterially into either the lingual or maxillary artery in 43 patients. Triple-phase continuous fast spin echo MRI was performed. Changes in blood water longitudinal relaxation rate (⊿R1) were measured in relation to imaging phase, type of artery, measurement site, and tumor size. Results : ⊿R1 was significantly higher at the tumor margin than at the center for both arteries, except in the first phase for the lingual artery. ⊿R1 was greatest in the third phase for the lingual artery and in the second phase for the maxillary artery. For both arteries, as the tumor size increased, there was a significant decrease in ⊿R1 at the center of the tumor compared to the margin. Conclusion : The factors associated with ⊿R1 were imaging phase, type of artery, measurement site, and tumor size. When determining a drug's optimal dose, the type of artery and tumor size must be taken into consideration.

We retrospectively evaluated the safety and effectiveness of an external carotid arterial sheath (ECAS) for intra-arterial chemotherapy (IACT) for locally advanced tongue cancer. Thirty-one patients with the Union for International Cancer Control’s 8th TNM stage III–IV tongue cancer underwent IACT using the ECAS combined with RT and systemic chemotherapy with either cisplatin and fluorouracil (FP) or docetaxel, cisplatin, and fluorouracil (TPF) between October 2015 and February 2021. The ECAS was inserted retrogradely via the superficial temporal artery, and the tip was placed in the external carotid artery between the maxillary and facial arteries. A microcatheter was inserted into each tumor-feeding artery through the ECAS under fluoroscopy, wherein cisplatin 50 mg/m2 was administered. IACT was performed weekly with neutralization using sodium thiosulfate. Complete response of the primary lesion was achieved in 28/31 (90%) patients. The median follow-up for all patients was 39 months. The 3-year overall survival, progression-free survival, and local control rates were 81.6%, 74.2%, and 83.4%, respectively. Grade 3 and greater toxicities included oral mucositis (45%), neutropenia (39%), nausea (13%), anemia (10%), thrombocytopenia (10%), dry mouth (10%), and fever (3%). There were no severe complications associated with IACT. In conclusion, the ECAS is feasible and effective for locally advanced tongue cancer.

Objective To assess the efficacy and safety of a covering method using polyglycolic acid (PGA) sheets and fibrin glue in preventing laryngopharyngeal bleeding after endoscopic laryngopharyngeal surgery (ELPS) combined with endoscopic submucosal dissection (ESD). Methods Twenty-one patients who underwent ELPS combined with ESD (28 resected pharyngeal carcinomas) were retrospectively evaluated. After completing ELPS combined with ESD, fibrinogen was sprayed onto the ulcer. A PGA sheet cut into 5 × 5 mm pieces that fit the size of the ELPS-induced ulcer was then placed over the ulcer and fixed in place with a fibrin glue comprising thrombin. Results The resection procedure was performed for all lesions. The median long diameter of the resected specimen was 36 mm. The rate of a resected specimen diameter >30 mm, use of anticoagulant/platelet, and macroscopic classification 0-Ⅱa were 68% (19/28), 19% (5/28), and 36% (10/28), respectively. The median time required to cover ELPS-induced ulcers using PGA sheets and fibrin glue was 10 min (range: 3–22 min). No post-ELPS bleeding, subcutaneous emphysema, or aspiration pneumonia (0/28) was observed. Conclusion The covering method using PGA sheets and fibrin glue for ELPS-induced ulcers is considered to be sufficiently safe and effective in preventing post-ELPS laryngopharyngeal bleeding. This method could be useful in preventing post-ELPS bleeding in patients with head and neck cancer.

Objective In cases of head and neck cancer treated with intra-arterial chemotherapy, no objective indices are available for determining the distribution of anticancer drugs administered to multiple arteries. To establish such indices, noninvasive measurements of drug concentrations are required in the arterial perfusion area of each artery. In MRI, changes in 1/T1 (Δ1/T1) are correlated with the contrast agent concentration. We focused on these properties and investigated whether it is possible to estimate anticancer drug concentrations within tissue based on Δ1/T1. Methods We employed the fast spin echo (FSE) sequence to determine optimum imaging parameters using a phantom. Subsequently, contrast agent was administered via the lingual and external carotid arteries for seven cases of tongue cancer. Δ1/T1 were then measured in tumor and nontumor tissues. The results of this study were compared with those of a previous study in which intratumor concentrations of anticancer agent were measured in excised specimens. Results The optimum imaging parameters for the FSE was two repetition times (TR, 500 and 1000 ms). When compared with the external carotid artery administration, the lingual artery administration of contrast agent resulted in significantly higher Δ1/T1 in both tumor and nontumor tissues (2.13 and 2.62 times, respectively). The multiplying factor for the nontumor tissue and high homogeneity of the contrast agent concentration were reasonably consistent with the results of the previous study. Conclusion This method can be applied to estimating intratissue concentrations of intra-arterially administered anticancer drugs, thus possibly providing useful information in determining the distribution of anticancer drugs.

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15–116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

Background The usefulness of particle therapy for skull base chordoma has not been established. The aim of this retrospective study was to analyse the treatment outcomes of proton therapy (PT) and carbon ion therapy (CIT) in patients with skull base chordoma at a single institution. Methods All patients who underwent PT or CIT with curative intent between 2003 and 2014 at Hyogo Ion Beam Medical Center were included in this study. Twenty-four patients were enrolled. Eleven (46%) received PT and 13 (54%) received CIT. Overall survival (OS), progression-free survival (PFS) and local control (LC) were calculated using the Kaplan–Meier method. Late toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. Results The median follow-up was 71.5 months (range, 14–175 months). The five-year LC, PFS and OS rates were 85, 81, and 86%, respectively. The LC (P = 0.048), PFS (P = 0.028) and OS (P = 0.012) were significantly improved in patients who had undergone surgery before particle therapy. No significant differences were observed in the LC rate and the incidence of grade 2 or higher late toxicities between patients who received PT and CIT. Conclusions Both PT and CIT appear to be effective and safe treatments and show potential to become the standard treatments for skull base chordoma. To increase the local control, surgery before particle therapy is preferable.

For doctors and other medical staff treating oral cancer, it is necessary to standardize the basic concepts and rules for oral cancer to achieve progress in its treatment, research, and diagnosis. Oral cancer is an integral part of head and neck cancer and is treated in accordance with the general rules for head and neck cancer. However, detailed rules based on the specific characteristics of oral cancer are essential. The objective of this article was to contribute to the development of the diagnosis, treatment, and research of oral cancer, based on the correct and useful medical information of clinical, surgical, pathological, and imaging findings accumulated from individual patients at various institutions. Our general rules were revised as the UICC was revised for the 8th edition and were published as the Japanese second edition in 2019. In this paper, the English edition of the “Rules” section is primarily presented.

Purpose Although proton therapy is controversial, it has been used to treat localized prostate cancer over the past 2 decades. The purpose of this study is to examine the long-term efficacy and toxicity of proton therapy for localized prostate cancer. Methods and Materials This was a retrospective observational study of 2021 patients from 2003 to 2014 at a single institution. Patients were classified using the risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019. Ninety-eight percent of the patients received 74 Gy (relative biological effectiveness) in 37 fractions. Fifty-one and 6% of the patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The outcomes were the time of freedom from biochemical relapse and the time to late toxicity by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. The outcomes were estimated using the Kaplan-Meier method and were analyzed using multivariable Cox proportional hazards models. Results The median follow-up period was 84 months (interquartile range, 60-110). The 5- and 10-year freedom from biochemical relapse rates were 100% and 100%, 99% and 88%, 93% and 86%, 90% and 79%, 88% and 68%, and 76% and 63% for the very low, low, favorable intermediate, unfavorable intermediate, high, and very high-risk groups, respectively. Patients with higher risk experienced biochemical relapse after shorter periods. The 5-year rates of grade 2 or higher late genitourinary and gastrointestinal toxicity were 2.2% and 4.0%, respectively. The results of multivariable analyses indicate that younger patients more often experienced biochemical relapse. Conclusions This study demonstrates the favorable biochemical controls of proton therapy even in advanced localized prostate cancer patients with a low incidence of late toxicities, supporting the feasibility of conducting prospective clinical trials. The risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019, are useful to classify patients with localized prostate cancer. Our findings might suggest the necessity to develop a treatment strategy that accounts for the patient’s age.

A single-isocenter half-beam technique is commonly used when irradiating the chest wall and supraclavicular regions in patients with high-risk breast cancer. However, several studies have reported that underdosage can occur at the junction of the chest wall and supraclavicular regions due to a "tongue-and-groove" effect. This study verified the efficacy of an open leaf technique (OL-tech) that involves placing a multileaf collimator 5 mm outside from the beam central axis to remove the effect of the multileaf collimator in a single-isocenter half-beam technique. We compared the junction doses of the OL-tech with those of a conventional technique (C-tech) in square and clinical plans, using 4 and 10 MV x-rays in the Clinac iX and 6 and 10 MV x-rays in the Trilogy accelerators (Varian Medical Systems, Palo Alto, CA). EBT3 radiochromic films were used for measurements. Measurements were performed at a depth of 3 cm when verifying field matching. The EBT3 films in the square plan indicated junction doses for the C-tech of 78.3% with the Clinac iX accelerator and 73.6% with the Trilogy accelerator. By contrast, the corresponding doses for the OL-tech were 107.2% and 99.8%, respectively. In the clinical plan, the junction doses for the C-tech were 76.5% with the Clinac iX accelerator and 72.6% with the Trilogy accelerator; the corresponding doses for the OL-tech were 108.3% and 101.7%, respectively. As with the square plan, variations in the junction dose were much smaller using the OL-tech than using the C-tech. Our results suggest that the OL-tech can be useful for improving dose homogeneity at the junction of the chest wall and supraclavicular regions.

Purpose To evaluate the optimal period of replanning to spare the rectal dose by investigating daily rectal movements during computed tomography (CT) image‐guided proton therapy for prostate cancer. Materials and methods To evaluate the optimum reference period for replanning, we analyzed 1483 sets of daily CT (dCT) images acquired from 40 prostate cancer patients and measured the daily rectal movement along the anterior–posterior direction based on the simulator CT (sCT) images and dCT images. We calculated daily dose distributions based on initial plans on the sCT images and replans on the dCT images for 13 representative patients, and evaluated daily dose volume histograms (DVHs) for the prostate, seminal vesicles, and rectum. Results The rectal anterior side on the dCT images around the seminal vesicles largely deviated toward the anterior side relative to the position on the reference sCT images, but the deviation decreased by referring to the dCT images and became nearly zero when we referred to the dCT images after 10‐day treatment. The daily DVH values for the prostate showed good dose coverage. For six patients showing rectal movement toward the anterior side, the daily rectal DVH (V77%) showed a 3.0 ± 1.7 cc excess from the initial plan and this excess was correlated with 9.9 ± 6.8 mm rectal movement. To identify the patients (37.5% in total) for whom the replanning on the 10th‐day and 20th‐day CT images reduced the V77% excess to 0.4 ± 1.5 cc and −0.2 ± 1.3 cc, respectively, we evaluated the accumulated mean doses with a 1.2 cc criterion. Conclusion Our data demonstrate that the daily movement of the rectal anterior side tends to move toward the anterior side, which results in a rectal overdose, and the mean of the movement gradually decreases with the passage of days. In such cases, replanning with the reference CT after 10 days is effective to spare the rectal dose.

Purpose This retrospective study aimed to determine the clinical outcomes following particle monotherapy (ie, proton therapy [PT] or carbon ion therapy [CIT]) in patients with sinonasal squamous cell carcinoma at a single institution. Methods and Materials Between August 2001 and March 2012, 59 patients were treated with definitive PT or CIT; none underwent chemotherapy or surgery. Of the patients, 22 (37%) had unresectable disease. PT was used in 38 patients (64%); CIT, 21 patients (36%). Almost half of the patients (n = 29, 47%) received 65.0 Gy (relative biological effectiveness) in 26 fractions. Results The median follow-up period was 30 months (range, 8-127 months) for all patients and 65 months (range, 9-127 months) for the survivors. The 3- and 5-year overall survival rates were 56.2% and 41.6%, respectively; progression-free survival rates, 42.9% and 34.7%, respectively; and local control rates, 54.0% and 50.4%, respectively. Late toxicities of grade ≥3 occurred in 13 patients (22%). Conclusions To our knowledge, this is the largest retrospective study of sinonasal squamous cell carcinoma treated with particle therapy alone. The efficacy of PT and CIT indicated that particle therapy can serve an important role in treating this disease.

PURPOSE We quantified interfractional movements of the prostate, seminal vesicles (SVs), and rectum during computed tomography (CT) image-guided proton therapy for prostate cancer and studied the range variation in opposed lateral proton beams. MATERIALS/METHODS We analyzed 375 sets of daily CT images acquired throughout the proton therapy treatment of ten patients. We analyzed daily movements of the prostate, SVs, and rectum by simulating three image-matching strategies: bone matching, prostate center (PC) matching, and prostate-rectum boundary (PRB) matching. In the PC matching, translational movements of the prostate center were corrected after bone matching. In the PRB matching, we performed PC matching and correction along the anterior-posterior direction to match the boundary between the prostate and the rectum's anterior region. In each strategy, we evaluated systematic errors (Σ) and random errors (σ) by measuring the daily movements of certain points on each anatomic structure. The average positional deviations in millimeter of each point were determined by the Van Herk formula of 2.5Σ + 0.7σ. Using these positional deviations, we created planning target volumes of the prostate and SVs and analyzed the daily variation in the water equivalent length (WEL) from the skin surface to the target along the lateral beam directions using the density converted from the daily CT number. Based on this analysis, we designed prostate cancer treatment planning and evaluated the dose volume histograms (DVHs) for these strategies. RESULTS The SVs' daily movements showed large variations over the superior-inferior direction, as did the rectum's anterior region. The average positional deviations of the prostate in the anterior, posterior, superior, inferior, and lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9, 9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9) (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5, 11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB matching showed the smallest positional deviations at all portions except for the anterior portion of the prostate and was able to markedly reduce the positional deviations at the posterior portion. The averaged WEL variations at the distal and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm, respectively, and showed the increasing of a few millimeters in PC and PRB matching compared to bone matching. In the treatment planning simulation, the DVH values of the rectum in PRB matching were reduced compared to those obtained with other matching strategies. CONCLUSION The positional deviations for the prostate on the posterior side and the SVs were smaller by PRB matching than the other strategies and effectively reduced the rectal dose. 3D dose calculations indicate that PRB matching with CT image guidance may do a better job relative to other positioning methods to effectively reduce the rectal complications. The WEL variation was quite large, and the appropriate margin (approx. 10 mm) must be adapted to the proton range in an initial planning to maintain the coverage of target volumes throughout entire treatment.

Purpose To evaluate the efficacy and safety of definitive proton beam therapy (PBT) for primary sacral chordoma. Methods and Materials We conducted a retrospective analysis of the clinical outcomes of eligible patients with primary sacral chordoma who had undergone definitive PBT with 70.4 Gy (relative biological effectiveness) in 32 fractions at our institution from September 2009 to October 2015. Local progression-free survival, distant metastasis-free survival, disease-free survival, cause-specific survival, and overall survival were evaluated. To explore the factors that influenced local progression, the following parameters were analyzed: sex, the presence of a spacer (Gore-Tex sheets), gross tumor volume, and extent of cranial tumor extension. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. To assess the impact of PBT on pain relief, the change in pain grades was investigated between the initiation of PBT and the last follow-up visit. Results Thirty-three eligible patients were analyzed. The median follow-up period was 37 months. The 3-year estimated local progression-free survival, distant metastasis-free survival, disease-free survival, cause-specific survival, and overall survival rates were 89.6%, 88.2%, 81.9%, 95.7%, and 92.7%, respectively. No significant association was between the patients’ clinicopathologic characteristics and local progression-free survival. Four patients developed grade 3 adverse events, including acute dermatitis (n = 1), ileus (n = 1), and pain due to sacral insufficiency fractures (n = 2). The pain grades had improved, were unchanged, or had deteriorated in 15, 7, and 11 patients, respectively. Conclusions Definitive PBT with 70.4 Gy (relative biological effectiveness) in 32 fractions is an effective treatment with acceptable toxicity for primary sacral chordoma and has the potential to reduce pain.

The aim of this retrospective study was to report long‐term clinical outcomes in patients treated with proton therapy (PT) for localized prostate cancer. Between 2001 and 2014, 1375 consecutive patients were treated with PT. Patients were classified into prognostic risk groups based on the National Comprehensive Cancer Network criteria. Freedom from biochemical relapse (FFBR), cancer‐specific survival (CSS) and incidence of late gastrointestinal (GI)/genitourinary (GU) toxicities were calculated. Multivariate analysis was performed to identify clinical prognostic factors for FFBR and late toxicities. The median follow‐up period was 70 months (range, 4–145 months). In total, 99% of patients received 74 Gy (relative biologic effectiveness [RBE]); 56% of patients received neoadjuvant androgen deprivation therapy. For the low‐, intermediate‐, high‐, and very high‐risk groups, 5‐year FFBR was 99% (95% confidence intervals [CI], 96–100%), 91% (95% CI, 88–93%), 86% (95% CI, 82–89%), and 66% (95% CI, 53–76%), respectively, and 5‐year CSS was 100% (95% CI, 100–100%), 100% (95% CI, 100–100%) , 99% (95% CI, 97–100%), and 95% (95% CI, 94–98%), respectively. Patient age, T classification, Gleason score, prostate‐specific antigen, and percentage of positive cores were significant prognostic factors for FFBR. Grade 2 or higher GI and GU toxicities were 3.9% and 2.0%. Patient age was a prognostic factor for both late GI and GU toxicities. This study represents the largest cohort of patients treated with PT for localized prostate cancer, with the longest follow‐up to date. Our results demonstrate that the biochemical control of PT is favorable particularly for high‐ and very high‐risk patients with lower late genitourinary toxicity and indicates the necessity of considering patient age in the treatment protocols.

The purpose of this study was to compare between superparamagnetic iron oxide (SPIO)-enhanced three-dimensional balanced turbo field-echo (B-TFE) sequence with T2 preparation pulse (T2 prep) and T2*-weighted imaging (T2*WI) for the simultaneous detection of hepatocellular carcinoma (HCC) and vessel thrombus. For 1.5-T magnetic resonance imaging, SPIO was administered to 23 patients with a portal or venous tumor thrombus, and B-TFE with T2 prep and T2*WI were acquired. Regions of interest in the B-TFE and T2*WI were selected for the tumor, liver, tumor thrombus, and vessels. The contrasts of the HCC in the liver and the tumor thrombus in the vessels were determined from clinical image. Contrast was calculated using the mean value of the signal intensity on the HCC to the liver and tumor thrombus to vessels. The mean contrasts between HCC and the liver with the use of B-TFE and T2*WI were 0.61 ± 0.05 and 0.70 ± 0.04, respectively. The contrast of HCC to the liver was significantly higher in T2*WI than in B-TFE (p

Summary Objective This study aims at selecting recipient vessels for free flap following intra-arterial chemoradiotherapy. At present, many centers combine intra-arterial chemotherapy and concomitant radiotherapy for treating head and neck cancer with favorable results. However, some patients develop recurrent, residual disease/complications after completing treatment protocols and thus require free-flap surgery. The feasibility of microsurgery following intra-arterial chemoradiotherapy remains unclear. Study design and methods We retrospectively analyzed 730 patients who underwent free-flap surgery for managing treatment-related complications/defects following head and neck surgery from January 1999 to February 2012. All patients were categorized into two groups according to the presence (group A)/absence (group B) of a history of intra-arterial chemotherapy. Microvascular revision rates were compared between the groups. In group A, the correlation between catheterization sites and recipient vessels used for microsurgery was assessed. Results A total of 769 free flaps were created in 730 patients and comprised 36 and 733 flaps in groups A and B, respectively. Microvascular revision rates were 2.8% (1/36) and 4.2% (31/733) in groups A and B, respectively, with no significant difference observed between the groups. No statistically significant difference was observed when only cases of arterial thrombosis were included. Vessels used for recipient anastomoses were not directly exposed to intra-arterially injected agents. Conclusion Preoperative intra-arterial chemoradiotherapy does not significantly increase the risk of microvascular revisions, particularly artery-related revisions, if vessels selectively catheterized and perfused with chemotherapeutic agents during intra-arterial chemotherapy are avoided as recipient vessels.

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15–116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

The aim of this study was to evaluate the efficacy and safety of proton beam therapy for patients with locally recurrent parotid cancer. Between 2009 and 2012, ten patients with locally recurrent parotid gland cancer were treated with proton beam therapy (70.2 Gy equivalents in 32 fractions) with or without intra-arterial infusion chemotherapy of cisplatin (50 mg/body/week, for a total of 5–8 weeks). The median follow-up was 24 months (range 10–49 months). The 1-year overall survival and local control rates were 80 %, and the 3-year overall survival and local control rates were 60 %. None of the patients experienced grade 3–5 toxicities in the treatment or the follow-up periods. These findings suggest that proton beam therapy could be applied effectively and safely for patients with locally recurrent parotid gland cancer.

Aim The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. Methods Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. Results For all patients, the median follow-up was 25 months (range, 3–77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. Conclusion Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer.

Background The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC). Methods Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6–74.8 GyE in 13–34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30–50 mg/body/week; docetaxel, 5–25 mg/body/week). Results One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively. Conclusion These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I–III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5‐fluorouracil (5‐FU) on days 1–5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X‐ray therapy and PBT. During the first half of the treatment, X‐rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow‐up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression‐free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3–4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment.

We developed an external carotid arterial sheath (ECAS) for performing intra-arterial chemotherapy (IACT) via the superficial temporal artery for head and neck cancer. This study aimed to assess the potential of a novel microcatheter with a steerable tip inserted through the ECAS in comparison to an existing hook-type microcatheter. The same operator used two types of microcatheters alternately for each weekly IACT session with the same patient, and the fluoroscopy time required for catheterization and the arterial selectivity of each microcatheter were compared. Ten patients with advanced head and neck cancer were enrolled. The steerable microcatheter significantly shortened the fluoroscopy time required for catheterization in comparison to the hook-type microcatheter (45.9 ± 4.8 vs 70.2 ± 9.8 s, p

Proton beam therapy (PBT), compared with conventional radiotherapy, can deliver high-dose radiation to a tumor, while minimizing doses delivered to surrounding normal tissues. The better dose distribution of PBT may contribute to the improvement in local control rate and reduction in late adverse events. We evaluated therapeutic results and toxicities of PBT combined with selective intra-arterial infusion chemotherapy (PBT-IACT) in patients with stage III–IVB squamous cell carcinoma of the tongue. After 2 systemic chemotherapy courses and whole-neck irradiation (36 Gy in 20 fractions), we administered concurrent chemoradiotherapy comprising PBT for the primary tumor [28.6–33 Gy(RBE) in 13–15 fractions] and for the metastatic neck lymph node [33–39.6 Gy(RBE) in 15–18 fractions] with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulfate. Between February 2009 and September 2012, 33 patients were enrolled. The median follow-up duration was 43 months. The 3-year overall survival, progression-free survival, local control rate, and regional control rate for the neck were 87.0, 74.1, 86.6, and 83.9 %, respectively. Major acute toxicities >grade 3 included mucositis in 26 cases (79 %), neutropenia in 17 cases (51 %), and dermatitis in 11 cases (33 %). Late grade 2 osteoradionecrosis was observed in 1 case (3 %). PBT-IACT for stage III–IVB tongue cancer has an acceptable toxicity profile and showed good treatment results. This protocol should be considered as a treatment option for locally advanced tongue cancer.

Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy.

To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0-2, 18-70 years-old, and sufficient organ function were eligible for this study. First, chemotherapy, consisting of 5-fluorouracil (800 mg/m(2) per 24 h on days 1-5) and cisplatin (100 mg/m(2) per 24 h on day 6), was administered, then a wide field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately. Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%) completed the course of treatment. The overall survival and the progression-free survival rates at 5 years were 78.04% (95% CI: 69.1~87.0%), and 68.74% (95% CI: 58.8~78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought to be promising. ALCRT will be considered to be a controlled trial to compare therapeutic results with those of concurrent chemoradiotherapy for NPC.

Background and purpose The aim of this study was to retrospectively analyse the outcomes of cases of adenoid cystic carcinomas (ACCs) of the head and neck that were treated at a single institution with particle therapy consisting of either protons or carbon ions. Methods and materials Between February 2002 and March 2012, 80 patients were treated with proton therapy (PT) or carbon ion therapy (CIT) alone. PT and CIT were employed in 40 (50%) patients each, and more than half of the patients received 65.0 GyE in 26 fractions ( n =47, 59%). Results The median duration of follow-up was 38months (range, 6–115months). For all patients, the 5-year for overall survival (OS) rate, progression-free survival (PFS) rate, and local control (LC) rate were 63%, 39%, and 75%, respectively. No significant differences between PT and CIT were observed. The 5-year LC rates for T4 and inoperable cases were 66% and 68%, respectively. Twenty-one patients (26%) experienced grade 3 or greater late toxicities, including three patients who developed grade 5 bleeding from nasopharyngeal ulcers. Conclusions Particle radiotherapy for ACC achieves favourable LC, and its efficacy in inoperable or T4 cases is promising. There were no significant differences between PT and CIT in terms of OS, PFS and LC.

Recent advances in highly conformal radiotherapies greatly extend the indications for radiotherapy of liver tumors. However, because of poor tolerance to hepatic radiation, estimation of the intensity of irradiation of the liver is important, particularly for a cirrhotic liver. Knowledge of radiation-induced hepatitis is important for understanding how to optimize hepatic radiation therapy. Pathological changes of the irradiated liver, which include perivenular fibrosis, sinusoidal obstruction, and damage to Kupffer cells and hepatocytes, can be visualized using clinical imaging techniques. This review article discusses and illustrates the pathological and radiological changes of hepatic tumors and the surrounding parenchyma of the irradiated liver.

Background Desmoid tumors, which are associated with familial adenomatous polyposis (FAP), tend to occur frequently in the abdominal wall and mesentery. Currently, there are no recognized treatments other than surgery, and frequent surgeries result in gastrointestinal obstructions and functional gastrointestinal disorders. Case presentation After surgery that was performed on a 39-year-old patient with FAP, we performed a second tumor excision which was the procedure used for frequently occurring mesenteric desmoid tumors. It was determined that the enlarged tumor would be difficult to operate on through an abdominal incision. Subsequently, the carbon ion radiotherapy of 50 Gy was then performed on the patient. Three years later, the tumor still remains reduced in size. In addition, we have not observed any negative effect on the digestive tract. Conclusions This is the first instance that the carbon ion radiotherapy has been effective for the unresected desmoid tumor, and it is believed that this will become the one effective option for the treatment of desmoid tumors.

Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors.Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B).Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS.Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.

Objective: The purpose of this study was to assess the outcome of alternating chemoradiotherapy in patients with high-risk cervical cancer. Methods: We performed definitive alternating chemoradiotherapy in cervical cancer patients with at least one high-risk factor such as International Federation of Gynecology and Obstetrics III or IVA disease, primary tumor diameter � 50 mm, positive pelvic node, and positive paraaortic node. Our chemoradiotherapy protocol was as follows: (i) alternating chemoradiotherapy with 5-fluorouracil and nedaplatin; (ii) whole pelvic radiotherapy with the dynamic conformal technique combined with intracavitary brachytherapy; (iii) prophylactic irradiation to the paraaortic region for International Federation of Gynecology and Obstetrics III/IVA or positive pelvic node and full-dose radiotherapy for positive para-aortic node. Between 1998 and 2010, 121 patients were treated with this protocol. Results: The median follow-up period was 53.7 months (7.6‐162.2). International Federation of Gynecology and Obstetrics stages were IB; (9.1%), IIA; 6 (5.0%), IIB; 53 (43.8%), IIIA; 7 (5.8%), IIIB; 37 (30.6%) and IVA; 7 (5.8%), respectively. Nodal involvement was reported in 77 patients (63.6%) at the pelvis and 25 (20.7%) at the para-aortic region. The 5-year overall survival and progression-free survival rates were 80.0 and 63.4%, respectively. Regarding Grade � 3 late toxicities, three patients developed urinary and three developed intestinal toxicities. We encountered no treatment-related death. Conclusions: The clinical results of our alternating chemoradiotherapy protocol for high-risk cervical cancer are promising.

The purpose of this study was to describe a novel system for treating advanced head and neck cancer consisting of an external carotid arterial sheath (ECAS) and a microcatheter to inject drugs retrogradely into multiple feeding arteries through the superficial temporal artery (STA). Four consecutive patients with head and neck cancer that had more than one feeding artery were enrolled in this study. The ECAS was made of polyurethane and surface-coated with heparin resin to prevent thrombus formation, allowing it to remain in place for a prolonged period of time. The ECAS was inserted through the STA, and its tip was placed between the maxillary artery and facial artery. The tumor-feeding arteries were selected using a hooked-shaped microcatheter through the ECAS. A total of 13 target arteries were selected in the four patients. The microcatheter inserted via the ECAS was used to catheterize ten arteries (five lingual arteries and five facial arteries). The remaining three lingual arteries were directly selected by the catheter without ECAS. All of the target arteries were able to be catheterized superselectively. The technical success rate was 100%. Vascular occlusion, which might have been caused by the ECAS, was observed in one patient. No neurologic toxicities occurred. This ECAS system is a new approach for retrograde superselective intra-arterial chemotherapy that covers the entire tumor with anticancer drugs. It has the potential to increase the effectiveness of therapy for advanced head and neck cancer. Level 4, Case Series.

Takahisa Kawamura, Keisuke Tomii, Yutaka Takahashi, Akihiko Okada, Yusuke Demizu, Nobukazu Fuwa, Yukihiro Imai Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan Department of Thoracic Surgery, Kobe City Medical Center General Hospital, Kobe, Japan Department of Gastrointestinal Medicine, Kobe City Medical Center General Hospital, Kobe, Japan Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Japan Department of Clinical Pathology, Kobe City Medical Center General Hospital, Kobe, Japan

Little is known about acute upper gastrointestinal (GI) complications associated with gemcitabine-concurrent proton radiotherapy (GPT) for inoperable pancreatic cancer. We investigated acute GI complications following GPT in patients with inoperable pancreatic cancer using small-bowel endoscopy. This prospective single center observational study was conducted at the Hyogo Ion Beam Medical Center from January 2010 to January 2012. Ninety-one patients who had clinically and medically inoperable pancreatic cancer treated by GPT were analyzed. Endoscopic examinations were performed before and after GPT to clarify the incidence rates of radiation-induced ulcers, GI hemorrhage, and GI perforation associated with GPT. Post-treatment endoscopic examinations revealed that 45 (49.4 %) patients had radiation-induced ulcers in the stomach and duodenum. Of those, many ulcerative lesions were found in the lower stomach (51 %) and horizontal part of the duodenum (39 %), regardless of the primary tumor site in the pancreas. Neither GI hemorrhage, nor perforation, was found in post-treatment endoscopy examinations. Approximately half of the patients treated with GPT for inoperable pancreatic cancer exhibited radiation-induced ulcers in the stomach and duodenum.

Introduction Although many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non–small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification. Methods From April 2003 to December 2009, 70 histologically confirmed patients were treated with proton ( n = 43) or carbon-ion ( n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0. Results The median follow-up period for living patients was 51 months (range, 24–103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients. Conclusion Particle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible.

Polymorphous low-grade adenocarcinoma is a rare malignant tumor that mainly occurs in salivary glands, particularly in the hard palate. To date, surgery has been the most commonly used treatment method with the aim of achieving negative margins of resection. Here, we report a case of a 51-year-old woman who presented with a painless growing mass in her oral cavity with Rouviere’s lymph node metastasis. Laboratory data showed severe anemia because of bleeding from the tumor. We inserted two catheters into the bilateral external carotid arteries via the superficial temporal arteries, and began continuous intra-arterial infusion with cisplatin and a cisplatin-neutralizing agent. The bleeding stopped after the first infusion, and we continued with weekly arterial cisplatin infusion and proton beam therapy (70.4 GyE in 32 fractions). A decrease in tumor volume has been maintained for 2 years, with no evidence of new metastasis.

Purpose To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. Methods and Materials From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). Results The median patient age was 67 years (range 18-87). The median planning target volume (PTV) was 455 cm 3 (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm 3 were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm 3 were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P Conclusions Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a longer follow-up period is needed to confirm these results.

The purpose of this study was to compare between superparamagnetic iron oxide (SPIO)-enhanced three-dimensional balanced turbo field-echo (B-TFE) sequence with T

It is recognized that the branches of the external carotid artery (ECA) can show variation, but the presence of a thyrolinguofacial trunk is extremely rare and always originates from the ECA. We report a case of the thyrolinguofacial trunk arising from the carotid bifurcation (CB) on the left side in a 76-year-old man with advanced tongue cancer, as revealed by three-dimensional computed tomography angiography for vascular mapping of the carotid vessels prior to superselective intra-arterial catheterization. The thyrolinguofacial trunk arose 1.6 mm below the CB from the anterior surface of the left CB. The inner diameter of the thyrolinguofacial trunk at origin was 4.4 mm and the angle between the thyrolinguofacial trunk and CB was 128°. After a 1.7-mm course, the trunk divided into the superior thyroid artery and a linguofacial trunk, the inner diameters of which were 1.5 and 3.4 mm, respectively, at origin. The angle between the two arteries was 88°. After a 9.8-mm course from the bifurcation, the linguofacial trunk divided into the lingual artery and facial artery, the inner diameters of which were 1.8 and 1.9 mm, respectively, at origin. The angle between the two arteries was 61°. It is important to recognize such an anatomic variation of the branches of the ECA prior to superselective intra-arterial catheterization or microsurgical reconstruction for head and neck cancer.

The purpose of this study is to assess the efficacy of alternating chemoradiation in patients with nasopharyngeal cancer. From 1990-2006, 100 patients with nasopharyngeal cancer were treated with alternating chemoradiation at the Aichi Cancer Center. Of these, 4, 2, 23, 34, 13 and 23 patients were staged as I, IIA, IIB, III, IVA and IVB, respectively. The median radiation doses for primary tumors and metastatic lymph nodes were 66.6 Gy (range, 50.4-80.2 Gy) and 66 Gy (range, 40.4-82.2 Gy), respectively. A total of 82 patients received chemotherapy with both cisplatin and 5-fluorouracil (5-FU), while 14 patients received nedaplatin (CDGP) and 5-FU. With a median follow-up of 65.9 months, the 5-year rates of overall survival (OAS) and progression-free survival (PFS) were 78.1% and 68.3%, respectively. On multivariate analysis (MVA), elderly age, N3, and WHO type I histology proved to be significantly unfavorable prognostic factors of OAS. As for PFS, there were T4, N3, and WHO type I histology in MVA. Acute toxicities of hematologic and mucositis/dermatitis ≥ Grade 3 were relatively high (32%); however, they were well-managed. Late toxicities of ≥ Grade 3 were three (3%) mandibular osteomyelitis and one (1%) lethal mucosal bleeding. Results for alternating chemoradiation for nasopharyngeal carcinoma are promising. In order to improve outcomes, usage of intensity-modulated radiation therapy and application of active anticancer agents are hopeful treatments, especially for groups with poor prognosis factors with WHO type I histopathology, T4 and/or N3 disease.

Background We planned a phase I study of weekly arterial infusion of docetaxel and cisplatin via a superficial temporal artery for recurrent head and neck cancer to determine the optimal dose. Methods The dose of cisplatin was fixed and the dose of docetaxel was escalated from 8 mg/m2, with an increase of 2 mg/m2 per step, to identify the maximum tolerated dose (MTD). In total, 4 courses of weekly chemotherapy were administered. Results Twelve patients were recruited to this trial. The MTD of docetaxel was 14 mg/m2. At this dose level, dose-limiting toxicity was observed in 2 of 3 patients. One patient experienced grade 3 leukopenia, while the other experienced grade 3 leukopenia. Myelosuppression was the dose-limiting toxicity for this regimen. Conclusion The recommended dose for weekly arterial infusion of docetaxel was identified as 12 mg/m2 combined with weekly cisplatin at 40 mg/m2, with 4 courses of each. © 2011 Wiley Periodicals, Inc. Head Neck, 2011